Takeda’s purchase was the world’s biggest announced acquisition of 2018, transforming the 237-year-old Japanese company into a top 10 drugmaker with lucrative therapies for rare diseases and a sizable footprint in the U.S.

It’s part of a larger shift in the industry as drugmakers scramble to consolidate, seeking to bulk up to survive the increasing pressure from stricter regulations on drug prices and looming patent expirations. Already in 2019, the Takeda deal has been trumped in size by Bristol-Myers Squibb Co.’s $74 billion agreement last week to buy Celgene Corp.

Takeda and Shire’s combined revenue catapult it into the ranks of the global pharmaceutical majors — the first Japanese company to reach the top 10. The new Takeda would have ranked as No. 9 among the biggest drugmakers by revenue, but Bristol-Myers’ deal with Celgene, if it succeeds, will push it down one notch. The company will also hold a unique position in being a big pharmaceutical company with a focus on rare diseases acquired from Shire’s portfolio.

One of the key drivers for the acquisition was to gain further exposure to the U.S., the world’s most profitable drug market. Japan hasn’t become a dependable source for growth, because of a shrinking population and regulatory pressure that has pushed down drug prices nearly every year. Although the U.S. also poses a drug-pricing risk, it’s one most pharma giants are willing to take for the revenue stream.

Takeda will contribute further to the dealmaking frenzy, thanks to the heavy debt load it has taken on. The company has laid out a scenario of a potential $10 billion in divestments in an effort to deleverage. Chief Executive Officer Christophe Weber said Monday investors should expect asset sales this year. The company is looking to divest non-core businesses outside Japan where the company is not an industry leader and does not have critical mass in the market.

According to the reports published in bloombergquint.com Takeda’s debt load was the issue that drew the biggest fire from critics of the deal, and caused Moody’s Investors Service to downgrade the company’s credit rating. Net borrowings will more than double to nearly five times earnings after it takes on about $30 billion in debt to acquire Shire, plus the debt on that company’s books. That’s compared to an industry average multiple of around one. The company has said it intends to deleverage to a debt ratio multiple of around two within five years.

Takeda’s stock price has fallen 26 percent since it announced its interest in acquiring Shire at the end of March 2018. When it eventually made its offer in May, Shire’s market valuation was higher than Takeda’s. The stock has struggled to find momentum amid technical pressures as managers shift their portfolios to account for Shire’s stock delisting and Takeda’s depository shares being listed on the New York Stock Exchange.

The shares rose as much as 2.9 percent in early Tokyo trading on Tuesday, after Takeda announced the deal closing and SMBC Nikko Securities upgraded the drugmaker, saying it was “heavily undervalued.” Takeda shares jumped 7.5 percent on Monday, for their biggest gain in almost three years.

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